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Miranda J, Key Wakate Teruya A, Leão Filho H, Lahan-Martins D, Tamura Sttefano Guimarães C, de Paula Reis Guimarães V, Ide Yamauchi F, Blasbalg R, Velloni FG. Diffuse and focal liver fat: advanced imaging techniques and diagnostic insights. Abdom Radiol (NY) 2024; 49:4437-4462. [PMID: 38896247 DOI: 10.1007/s00261-024-04407-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2024] [Revised: 05/21/2024] [Accepted: 05/22/2024] [Indexed: 06/21/2024]
Abstract
The fatty liver disease represents a complex, multifaceted challenge, requiring a multidisciplinary approach for effective management and research. This article uses conventional and advanced imaging techniques to explore the etiology, imaging patterns, and quantification methods of hepatic steatosis. Particular emphasis is placed on the challenges and advancements in the imaging diagnostics of fatty liver disease. Techniques such as ultrasound, CT, MRI, and elastography are indispensable for providing deep insights into the liver's fat content. These modalities not only distinguish between diffuse and focal steatosis but also help identify accompanying conditions, such as inflammation and fibrosis, which are critical for accurate diagnosis and management.
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Affiliation(s)
- Joao Miranda
- Department of Radiology, Memorial Sloan Kettering Cancer Center, 1275 York Ave, New York, NY, 10065, USA.
- Department of Radiology, University of São Paulo, R. Dr. Ovídio Pires de Campos, 75-Cerqueira César, São Paulo, SP, 05403-010, Brazil.
| | - Alexandre Key Wakate Teruya
- Department of Radiology, Diagnósticos da América SA (DASA), Av Juruá 434, Alphaville Industrial, Barueri, São Paulo, SP, 06455-010, Brazil
| | - Hilton Leão Filho
- Department of Radiology, Diagnósticos da América SA (DASA), Av Juruá 434, Alphaville Industrial, Barueri, São Paulo, SP, 06455-010, Brazil
| | - Daniel Lahan-Martins
- Department of Radiology, Diagnósticos da América SA (DASA), Av Juruá 434, Alphaville Industrial, Barueri, São Paulo, SP, 06455-010, Brazil
- Departament of Radiology-FCM, State University of Campinas (UNICAMP), R. Tessália Vieira de Camargo, 126 Cidade Universitária, Campinas, SP, 13083-887, Brazil
| | - Cássia Tamura Sttefano Guimarães
- Department of Radiology, Diagnósticos da América SA (DASA), Av Juruá 434, Alphaville Industrial, Barueri, São Paulo, SP, 06455-010, Brazil
| | - Vivianne de Paula Reis Guimarães
- Department of Radiology, Diagnósticos da América SA (DASA), Av Juruá 434, Alphaville Industrial, Barueri, São Paulo, SP, 06455-010, Brazil
| | - Fernando Ide Yamauchi
- Department of Radiology, Diagnósticos da América SA (DASA), Av Juruá 434, Alphaville Industrial, Barueri, São Paulo, SP, 06455-010, Brazil
| | - Roberto Blasbalg
- Department of Radiology, Diagnósticos da América SA (DASA), Av Juruá 434, Alphaville Industrial, Barueri, São Paulo, SP, 06455-010, Brazil
| | - Fernanda Garozzo Velloni
- Department of Radiology, Diagnósticos da América SA (DASA), Av Juruá 434, Alphaville Industrial, Barueri, São Paulo, SP, 06455-010, Brazil
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Di Sessa A, Passaro AP, Colasante AM, Cioffi S, Guarino S, Umano GR, Papparella A, Miraglia Del Giudice E, Marzuillo P. Kidney damage predictors in children with metabolically healthy and metabolically unhealthy obesity phenotype. Int J Obes (Lond) 2023; 47:1247-1255. [PMID: 37689826 DOI: 10.1038/s41366-023-01379-1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2022] [Revised: 08/25/2023] [Accepted: 08/30/2023] [Indexed: 09/11/2023]
Abstract
BACKGROUND Obesity and kidney damage have been closely linked in adults, but little is still known in childhood. OBJECTIVE To identify predictors of kidney damage in children with metabolically healthy (MHO) and metabolically unhealthy (MUO) obesity phenotypes. METHODS We retrospectively examined 396 children with obesity (mean age 10.72 ± 2.71 years, body mass index-standard deviation score, BMI-SDS, 2.23 ± 0.57) stratified according to metabolic phenotypes. Kidney damage was defined as the presence of reduced estimated glomerular filtration rate (eGFR < 90 mL/min/1.73m2) and/or albuminuria (≥ 30 mg/g urinary creatinine). RESULTS Kidney damage was found in 20.9% of the study population. Children with kidney damage had higher BMI-SDS, homeostasis model assessment of insulin resistance (HOMA-IR), and inflammation markers levels and increased prevalence of non-alcoholic fatty liver disease (NAFLD) than those without kidney damage (all p < 0.005). MUO and MHO subjects had respectively an odds ratio (OR) to show kidney damage of of 1.92 (95%CI:1.22-3.01; p = 0.005) and 1.05 (95%CI:1.00-1.09; p = 0.028) after adjustments. Moreover, we found that only HOMA-IR was closely associated to kidney damage in MUO group (OR = 2.07;95%CI:1.20-3.57; p = 0.007), while HOMA-IR (OR = 1.15;95%CI:1.02-1.29; p = 0.011) and uric acid (OR = 1.15;95% CI:1.02-1.30; p = 0.010) were the only significant risk factors for kidney damage in MHO group. CONCLUSION An increased risk of kidney damage has been observed in children with obesity and in particular in those with MUO phenotype. As their role on kidney function, HOMA-IR should be monitored in MUO children and both HOMA-IR and uric acid in MHO children.
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Affiliation(s)
- Anna Di Sessa
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy.
| | - Antonio Paride Passaro
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Alberto Maria Colasante
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | | | - Stefano Guarino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Giuseppina Rosaria Umano
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Alfonso Papparella
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Emanuele Miraglia Del Giudice
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
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Di Sessa A, Cembalo Sambiase Sanseverino N, De Simone RF, Marrapodi MM, Cirillo G, Umano GR, Guarino S, Papparella A, Miraglia Del Giudice E, Marzuillo P. Association between non-alcoholic fatty liver disease and subclinical hypothyroidism in children with obesity. J Endocrinol Invest 2023; 46:1835-1842. [PMID: 36828986 DOI: 10.1007/s40618-023-02041-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2022] [Accepted: 02/10/2023] [Indexed: 02/26/2023]
Abstract
PURPOSE We aimed (i) evaluating the relationship between non-alcoholic fatty liver disease (NAFLD) and thyroid function tests, (ii) testing if the relationship between NAFLD and thyroid dysfunction could be driven by the obesity and the IR degree, and (iii) exploring the influence of the patatin-like phospholipase domain-containing protein-3 (PNPLA3) I148M and the transmembrane 6 superfamily member 2 (TM6SF2) E167K polymorphisms on the association between NAFLD and thyroid function in children. METHODS We examined 2275 children and adolescents with obesity. Subclinical hypothyroidism (SH) was defined by thyroid-stimulating hormone (TSH) > 4.2 μUI/ml with normal fT3 and fT4. RESULTS Children with NAFLD showed higher SH prevalence than those without NAFLD (15.7% Vs 7.4%;p = 0.001) and showed an adjusted odds ratio (aOR) to have SH of 1.68 (95% CI:1.01-2.80;p = 0.04) while patients with SH had an aOR to show NAFLD of 2.13(95% CI:1.22-3.73;p = 0.008). Patients having severe obesity and IR degree presented an aOR to show both NAFLD and SH of 3.61 (95% CI:1.78-7.33;p < 0.0001). Subjects with NAFLD carrying the TM6SF2 167 K allele had lower TSH levels than non-carriers (p = 0.03) and showed an aOR to have SH of 0.10 (95% CI: 0.01-0.79;p = 0.02). No differences were found in carriers of the PNPLA3 148 M allele. A general linear model for TSH variance showed a significant association of TSH with TM6SF2 genotypes only in the NAFLD group (p = 0.001). CONCLUSION Children with obesity and NAFLD presented increase risk of SH and vice versa likely due to the adverse effect of duration of obesity, obesity degree, and IR. The TM6SF2 E167K exerts a protective role against SH in children with obesity and NAFLD.
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Affiliation(s)
- A Di Sessa
- Department of Woman, Child and of General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via L. De Crecchio no 2, 80138, Naples, Italy.
| | - N Cembalo Sambiase Sanseverino
- Department of Woman, Child and of General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via L. De Crecchio no 2, 80138, Naples, Italy
| | - R F De Simone
- Department of Woman, Child and of General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via L. De Crecchio no 2, 80138, Naples, Italy
| | - M M Marrapodi
- Department of Woman, Child and of General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via L. De Crecchio no 2, 80138, Naples, Italy
| | - G Cirillo
- Department of Woman, Child and of General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via L. De Crecchio no 2, 80138, Naples, Italy
| | - G R Umano
- Department of Woman, Child and of General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via L. De Crecchio no 2, 80138, Naples, Italy
| | - S Guarino
- Department of Woman, Child and of General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via L. De Crecchio no 2, 80138, Naples, Italy
| | - A Papparella
- Department of Woman, Child and of General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via L. De Crecchio no 2, 80138, Naples, Italy
| | - E Miraglia Del Giudice
- Department of Woman, Child and of General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via L. De Crecchio no 2, 80138, Naples, Italy
| | - P Marzuillo
- Department of Woman, Child and of General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Via L. De Crecchio no 2, 80138, Naples, Italy
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Stepan MD, Vintilescu ȘB, Streață I, Podeanu MA, Florescu DN. The Role of Vitamin D in Obese Children with Non-Alcoholic Fatty Liver Disease and Associated Metabolic Syndrome. Nutrients 2023; 15:2113. [PMID: 37432275 DOI: 10.3390/nu15092113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2023] [Revised: 04/20/2023] [Accepted: 04/26/2023] [Indexed: 07/12/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents a complex chronic condition, which in the absence of screening-monitoring markers and effective standardized treatment is one of the most important issues in pediatric pathology. In this study, we analyzed the role of vitamin D supplementation in obese children with/without NAFLD and the impact on the components of the associated metabolic syndrome (MS). The study included 22 children with simple obesity (SO) and 50 with NAFLD, aged between 6 and 14 years, who received regimen-based therapy or vitamin D supplementation in case of deficiency. Anthropometric and paraclinical data associated with MS were statistically compared before and after treatment. It was observed that there was a statistical association of NAFLD with MS components, which were present both in SO and in the 6-9 years group. Vitamin D deficiency was associated with the presence of obesity, NAFLD and MS components, and correction of the deficiency induced a tendency to normalize the associated parameters. In the case of a treatment strictly based on the regimen, we found decreases in vitamin D values and additional alteration of some parameters. Supplementation with vitamin D potentiates the effects of the specific regimen, and the effects seem to be dependent on the MS components.
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Affiliation(s)
- Mioara Desdemona Stepan
- Department of Infant Care-Pediatrics-Neonatology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Ștefănița Bianca Vintilescu
- Department of Infant Care-Pediatrics-Neonatology, University of Medicine and Pharmacy of Craiova, 200349 Craiova, Romania
| | - Ioana Streață
- Laboratory of Human Genomics, University of Medicine and Pharmacy of Craiova, 200638 Craiova, Romania
| | | | - Dan Nicolae Florescu
- Research Center of Gastroenterology and Hepatology, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania
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Wang H, Wang Q, Liang C, Pan L, Hu H, Fang H. Acupuncture improved hepatic steatosis in HFD-induced NAFLD rats by regulating intestinal microbiota. Front Microbiol 2023; 14:1131092. [PMID: 37007509 PMCID: PMC10061080 DOI: 10.3389/fmicb.2023.1131092] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2023] [Accepted: 02/28/2023] [Indexed: 03/18/2023] Open
Abstract
BackgroundIntestinal dysbiosis has been increasingly implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Acupuncture has been shown to have beneficial effects on NAFLD, but the mechanism is not yet clear. This study explores the potential beneficial effects of acupuncture on intestinal microbiota in NAFLD.MethodsAn NAFLD model in Sprague Dawley rats was established using a high-fat diet (HFD) for 10 weeks. NAFLD rats were randomly divided into control, model, and acupuncture groups. Following acupuncture treatment over 6 weeks, automated biochemical analysis was used to measure serum lipid metabolism parameters, including levels of alanine transferase, aspartate transferase, alkaline phosphatase, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The level of serum inflammatory factors interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) were measured by enzyme-linked immunosorbent assay. The characteristics of steatosis were evaluated using quantitative computed tomography, hematoxylin and eosin staining, and Oil Red O staining in the liver, while the intestinal microbiota was determined using 16S rRNA gene sequencing.ResultsAcupuncture decreased the systemic inflammatory response, ameliorated dyslipidemia, and improved liver function indexes in NAFLD model rats. Tomography and staining indicated that acupuncture reduced steatosis and infiltration of inflammatory cells in the liver. 16S rRNA analysis showed that acupuncture reduced the Firmicutes to Bacteroidetes (F/B) ratio, increased the abundance of microbiota, including Bacteroidales_S24-7_group, Prevotellaceae, Bacteroidaceae, Blautia, norank_f_Bacteroidales_S24-7_group, Bacteroides, and Prevotella_9, and decreased the abundance of Ruminococcaceae_UCG-014. Correlation analysis suggested a close correlation between lipid metabolism, inflammation factors, hepatic steatosis, and the changed intestinal microbiota.ConclusionAcupuncture can significantly improve lipid metabolism and the systemic inflammatory response in HFD-induced NAFLD rats, potentially by regulating intestinal microbiota composition.
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Affiliation(s)
- Haiying Wang
- Department of Cardiology, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Qiang Wang
- Chinese People’s Liberation Army Center of Disease Control and Prevention, Beijing, China
| | - Cuimei Liang
- Department of Acupuncture, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Liang Pan
- Department of Acupuncture, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Hui Hu
- Department of Acupuncture, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, China
- *Correspondence: Hui Hu,
| | - Hongjuan Fang
- Department of Endocrinology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
- Hongjuan Fang,
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Valentino MS, Marzuillo P, Esposito C, Bartiromo M, Nardolillo M, Villani AV, Maresca A, Furcolo G, Guarino S, Miraglia del Giudice E, Di Sessa A. The Impact of COVID-19 Pandemic Lockdown on the Relationship between Pediatric MAFLD and Renal Function. J Clin Med 2023; 12:2037. [PMID: 36902824 PMCID: PMC10003972 DOI: 10.3390/jcm12052037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/31/2022] [Revised: 02/26/2023] [Accepted: 03/03/2023] [Indexed: 03/08/2023] Open
Abstract
BACKGROUND Both direct and indirect effects of COVID-19 have been found in all age groups. In particular, adult data demonstrated significant changes in patients with chronic and metabolic disease (e.g., obesity, diabetes, chronic kidney disease (CKD), and metabolic associated fatty liver dysfunction (MAFLD)), while similar pediatric evidence is still limited. We aimed at investigating the impact of the COVID-19 pandemic lockdown on the relationship between MAFLD and renal function in children with CKD due to congenital abnormalities of the kidney and urinary tract (CAKUT). METHODS A total of 21 children with CAKUT and CKD ≥ stage 1 underwent a comprehensive evaluation within 3 months before and 6 months after the first Italian lockdown. RESULTS At follow-up, CKD patients with MAFLD presented higher BMI-SDS, serum uric acid, triglycerides, and microalbuminuria levels and lower eGFR levels than those without MAFLD (all p < 0.05). Higher ferritin and white blood cell concentrations were also found in patients with CKD diagnosed with MAFLD than peers without MAFLD (both p = 0.01). Compared to children without MAFLD, a higher delta of BMI-SDS, eGFR levels, and microalbuminuria levels was found in patients with MAFLD. CONCLUSIONS Due to the negative influence of the COVID-19 lockdown on cardiometabolic health in childhood, a careful management of children with CKD is warranted.
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Affiliation(s)
- Maria Sole Valentino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Claudia Esposito
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Mario Bartiromo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Michele Nardolillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Annalisa Valentina Villani
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Alessandro Maresca
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Giuseppe Furcolo
- Unità Operativa Complessa di Pediatria e Pronto Soccorso Pediatrico, AORN Moscati, 83100 Avellino, Italy
| | - Stefano Guarino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Emanuele Miraglia del Giudice
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
| | - Anna Di Sessa
- Department of Woman, Child, and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy
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Di Bonito P, Di Sessa A, Licenziati MR, Corica D, Wasniewska M, Umano GR, Morandi A, Maffeis C, Faienza MF, Mozzillo E, Calcaterra V, Franco F, Maltoni G, Valerio G. Is Metabolic Syndrome Useful for Identifying Youths with Obesity at Risk for NAFLD? CHILDREN (BASEL, SWITZERLAND) 2023; 10:children10020233. [PMID: 36832363 PMCID: PMC9955487 DOI: 10.3390/children10020233] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/22/2022] [Revised: 01/23/2023] [Accepted: 01/26/2023] [Indexed: 01/31/2023]
Abstract
The definition of metabolic syndrome (MetS) in childhood is controversial. Recently, a modified version of the International Diabetes Federation (IDF) definition was proposed using reference data from an international population for high waist circumference (WC) and blood pressure (BP), while the fixed cutoffs for lipids and glucose were not changed. We analyzed MetS prevalence using this modified definition (MetS-IDFm) and its association with non-alcoholic fatty liver disease (NAFLD) in 1057 youths (age 6-17 years) with overweight/obesity (OW/OB). A comparison with another modified definition of MetS according to the Adult Treatment Panel III (MetS-ATPIIIm) was performed. The prevalence of MetS-IDFm was 27.8% and 28.9% by MetS-ATPIIIm. The Odds (95% Confidence Intervals) of NAFLD was 2.70 (1.30-5.60) (p = 0.008) for high WC, 1.68 (1.25-2.26)(p = 0.001) for MetS, 1.54 (1.12-2.11)(p = 0.007) for low HDL-Cholesterol, 1.49 (1.04-2.13)(p = 0.032) for high triglycerides and 1.37 (1.03-1.82)(p = 0.033) for high BP. No substantial difference was found in the prevalence of MetS-IDFm and frequency of NAFLD compared to Mets-ATPIIIm definition. Our data demonstrate that one third of youths with OW/OB have MetS, whichever was the criterion. Neither definition was superior to some of their components in identifying youths with OW/OB at risk for NAFLD.
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Affiliation(s)
- Procolo Di Bonito
- Department of Internal Medicine, “S. Maria delle Grazie” Hospital, 80078 Pozzuoli, Italy
| | - Anna Di Sessa
- Department of Woman, Child and of General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Napoli, Italy
| | - Maria Rosaria Licenziati
- Neuro-Endocrine Diseases and Obesity Unit, Department of Neurosciences, Santobono-Pausilipon Children’s Hospital, 80122 Napoli, Italy
| | - Domenico Corica
- Department of Human Pathology in Adulthood and Childhood, University of Messina, 98122 Messina, Italy
| | - Malgorzata Wasniewska
- Department of Human Pathology in Adulthood and Childhood, University of Messina, 98122 Messina, Italy
| | - Giuseppina Rosaria Umano
- Department of Woman, Child and of General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Napoli, Italy
| | - Anita Morandi
- Department of Surgery, Dentistry, Pediatrics and Gynecology, Section of Pediatric Diabetes and Metabolism, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37134 Verona, Italy
| | - Claudio Maffeis
- Department of Surgery, Dentistry, Pediatrics and Gynecology, Section of Pediatric Diabetes and Metabolism, University and Azienda Ospedaliera Universitaria Integrata of Verona, 37134 Verona, Italy
| | - Maria Felicia Faienza
- Department of Precision and Regenerative Medicine and Ionian Area, University of Bari “Aldo Moro”, 70124 Bari, Italy
| | - Enza Mozzillo
- Department of Translational Medical Science, Section of Pediatrics, Regional Center of Pediatric Diabetes, University of Naples “Federico II”, 80131 Napoli, Italy
| | - Valeria Calcaterra
- Pediatric Department, Buzzi Children’s Hospital, 20154 Milano, Italy
- Department of Internal Medicine, University of Pavia, 27100 Pavia, Italy
| | - Francesca Franco
- Pediatric Department, Azienda Sanitaria Universitaria Friuli Centrale, Hospital of Udine, 33100 Udine, Italy
| | - Giulio Maltoni
- Pediatric Unit, IRCCS Azienda Ospedaliero-Universitaria di Bologna, 40138 Bologna, Italy
| | - Giuliana Valerio
- Department of Movement Sciences and Wellbeing, University of Napoli “Parthenope”, 80133 Napoli, Italy
- Correspondence:
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Di Sessa A, Russo MC, Arienzo MR, Umano GR, Cozzolino D, Cirillo G, Guarino S, Miraglia Del Giudice E, Marzuillo P. PNPLA3 I148M Polymorphism Influences Renal Function in Children With Obesity and Prediabetes. J Ren Nutr 2022; 32:670-676. [PMID: 35121131 DOI: 10.1053/j.jrn.2022.01.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2021] [Revised: 11/28/2021] [Accepted: 01/10/2022] [Indexed: 11/11/2022] Open
Abstract
OBJECTIVE Nonalcoholic fatty liver disease negatively impacts on renal function with the contribution of the I148 M variant in the patatin-like phospholipase-containing domain 3 (PNPLA3) gene. We hypothesized that children with prediabetes present with a lower estimated glomerular filtration rate (eGFR) than those with normal glucose tolerance (NGT) and that the 148M PNPLA3 allele could play a worsening role. We aimed evaluating the influence of the I148 M PNPLA3 polymorphism on the relationship between the eGFR and prediabetes in children with obesity. METHODS One thousand thirty-six children underwent to complete assessment and were genotyped for the I148 M PNPLA3 polymorphism. RESULTS Patients with prediabetes showed lower eGFR levels (171.03 ± 40.32 vs. 190.80 ± 41.71 mL/min/1.73 m2; P = .001) and higher prevalence of nonalcoholic fatty liver disease (80% vs. 59%; P = .003) than those with NGT. Children with prediabetes showed lower eGFR levels than those with NGT (150.97 ± 14.56 vs. 192.88 ± 40.09; P < .0001) among carriers of the PNPLA3 148M allele. This was not confirmed among patients homozygous for the PNPLA3 I148 allele. A general linear model for eGFR variance confirmed an inverse and significant association of the eGFR with prediabetes in patients carrying the 148M PNPLA3 allele but not in patients homozygous for the PNPLA3 I148 allele. CONCLUSIONS Prediabetes negatively affects renal function in children with obesity. This effect is heightened in patients carrying the PNPLA3 148M allele.
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Affiliation(s)
- Anna Di Sessa
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy.
| | - Maria Cecilia Russo
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Maria Rosaria Arienzo
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Giuseppina Rosaria Umano
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Domenico Cozzolino
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Grazia Cirillo
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Stefano Guarino
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Emanuele Miraglia Del Giudice
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania "Luigi Vanvitelli", Napoli, Italy
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Riccio S, Melone R, Vitulano C, Guida P, Maddaluno I, Guarino S, Marzuillo P, Miraglia del Giudice E, Di Sessa A. Advances in pediatric non-alcoholic fatty liver disease: From genetics to lipidomics. World J Clin Pediatr 2022; 11:221-238. [PMID: 35663007 PMCID: PMC9134151 DOI: 10.5409/wjcp.v11.i3.221] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/30/2021] [Revised: 08/05/2021] [Accepted: 04/02/2022] [Indexed: 02/06/2023] Open
Abstract
As a result of the obesity epidemic, non-alcoholic fatty liver disease (NAFLD) represents a global medical concern in childhood with a closely related increased cardiometabolic risk. Knowledge on NAFLD pathophysiology has been largely expanded over the last decades. Besides the well-known key NAFLD genes (including the I148M variant of the PNPLA3 gene, the E167K allele of the TM6SF2, the GCKR gene, the MBOAT7-TMC4 rs641738 variant, and the rs72613567:TA variant in the HSD17B13 gene), an intriguing pathogenic role has also been demonstrated for the gut microbiota. More interestingly, evidence has added new factors involved in the "multiple hits" theory. In particular, omics determinants have been highlighted as potential innovative markers for NAFLD diagnosis and treatment. In fact, different branches of omics including metabolomics, lipidomics (in particular sphingolipids and ceramides), transcriptomics (including micro RNAs), epigenomics (such as DNA methylation), proteomics, and glycomics represent the most attractive pathogenic elements in NAFLD development, by providing insightful perspectives in this field. In this perspective, we aimed to provide a comprehensive overview of NAFLD pathophysiology in children, from the oldest pathogenic elements (including genetics) to the newest intriguing perspectives (such as omics branches).
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Affiliation(s)
- Simona Riccio
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Rosa Melone
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Caterina Vitulano
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Pierfrancesco Guida
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Ivan Maddaluno
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Stefano Guarino
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Emanuele Miraglia del Giudice
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Anna Di Sessa
- Department of Woman, Child, General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
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10
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Di Sessa A, Guarino S, Melone R, De Simone RF, Marzuillo P, Miraglia del Giudice E. Relationship between nonalcoholic fatty liver disease and chronic kidney disease could start in childhood. World J Gastroenterol 2021; 27:5793-5795. [PMID: 34629802 PMCID: PMC8473591 DOI: 10.3748/wjg.v27.i34.5793] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2021] [Revised: 06/21/2021] [Accepted: 08/06/2021] [Indexed: 02/06/2023] Open
Abstract
The relationship between nonalcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) has gained considerable scientific interest in adults over the past few years. However, this association has recently emerged in children. Several published studies have suggested a role for NAFLD as a risk factor for CKD from the earliest age, with a potential influence of the major NAFLD risk polymorphisms, resulting in an increased risk of both cardiovascular and metabolic diseases. In view of the progressive course and increased cardiometabolic risk closely related to NAFLD and CKD, we focused on the link between these diseases in childhood.
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Affiliation(s)
- Anna Di Sessa
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Stefano Guarino
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Rosa Melone
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Rossella Francesca De Simone
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Emanuele Miraglia del Giudice
- Department of Woman, Child, and General and Specialized Surgery, University of Campania Luigi Vanvitelli, Naples 80138, Italy
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11
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Di Sessa A, Guarino S, Passaro AP, Liguori L, Umano GR, Cirillo G, Miraglia Del Giudice E, Marzuillo P. NAFLD and renal function in children: is there a genetic link? Expert Rev Gastroenterol Hepatol 2021; 15:975-984. [PMID: 33851883 DOI: 10.1080/17474124.2021.1906649] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/28/2021] [Accepted: 03/18/2021] [Indexed: 02/06/2023]
Abstract
Introduction: Over the past decades, a large amount of both adult and pediatric data has shown relationship between Nonalcoholic Fatty Liver Disease (NAFLD) and chronic kidney disease (CKD), resulting in an overall increased cardiometabolic burden. In view of the remarkable role of the genetic background in the NAFLD pathophysiology, a potential influence of the major NAFLD polymorphisms (e.g. the I148M variant of the Patatin-like phospholipase containing domain 3 (PNPLA3) gene, the E167K allele of the Transmembrane 6 superfamily member 2 (TM6SF2), the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13), and the Membrane bound O-acyltransferase domain containing 7-transmembrane channel-like 4 (MBOAT7-TMC4) genes) on renal function has been supposed. A shared metabolic and proinflammatory pathogenesis has been hypothesized, but the exact mechanism is still unknown.Areas covered: We provide a comprehensive review of the potential genetic link between NAFLD and CKD in children. Convincing both adult and pediatric evidence supports this association, but there is some dispute especially in childhood.Expert opinion: Evidence supporting a potential genetic link between NAFLD and CKD represents an intriguing aspect with a major clinical implication because of its putative role in improving strategy programs to counteract the higher cardiometabolic risk of these patients.
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Affiliation(s)
- Anna Di Sessa
- Department of Woman Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Stefano Guarino
- Department of Woman Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Antonio Paride Passaro
- Department of Woman Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Laura Liguori
- Department of Woman Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Giuseppina Rosaria Umano
- Department of Woman Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Grazia Cirillo
- Department of Woman Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Emanuele Miraglia Del Giudice
- Department of Woman Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Pierluigi Marzuillo
- Department of Woman Child and of General and Specialized Surgery, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
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12
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Di Sessa A, Guarino S, Umano GR, Arenella M, Alfiero S, Quaranta G, Miraglia del Giudice E, Marzuillo P. MAFLD in Obese Children: A Challenging Definition. CHILDREN (BASEL, SWITZERLAND) 2021; 8:247. [PMID: 33806784 PMCID: PMC8005020 DOI: 10.3390/children8030247] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 03/19/2021] [Accepted: 03/20/2021] [Indexed: 12/11/2022]
Abstract
BACKGROUND Recently, the new definition of Metabolic (dysfunction) associated fatty liver disease (MAFLD) has gained remarkable scientific interest. We aimed to evaluate the effectiveness of MAFLD definition in selecting obese children at higher cardiovascular risk. METHODS A total of 954 obese children and adolescents was retrospectively enrolled. Clinical, biochemical, and metabolic evaluations were performed. Hepatic steatosis was assessed by liver ultrasound. According to the metabolic status, the population was divided in three groups. Group 1 included obese patients without both non-alcoholic fatty liver disease (NAFLD) and metabolic dysregulation; group 2 included patients with obesity and NAFLD (then encompassing one MAFLD criterion); group 3 included patients with obesity, NAFLD and evidence of metabolic dysregulation (then encompassing more than 1 MAFLD criteria). RESULTS Patients of Group 3 showed a worse cardiometabolic profile, as also proven by the higher percentage of prediabetes (defined as the presence of impaired fasting glucose or impaired glucose tolerance) compared to other groups (p = 0.001). CONCLUSIONS MAFLD criteria in obese children seem to be less accurate in identifying patients having an intrinsic higher cardiometabolic risk. This suggests the need for a more accurate definition in the context of pediatric obesity.
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Affiliation(s)
| | | | - Giuseppina Rosaria Umano
- Department of Woman, Child and of General and Specialized Surgery, Università degli Studi della Campania “Luigi Vanvitelli”, Via Luigi De Crecchio 2, 80138 Napoli, Italy; (A.D.S.); (S.G.); (M.A.); (S.A.); (G.Q.); (E.M.d.G.); (P.M.)
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13
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Mosca A, Panera N, Crudele A, Alisi A. Noninvasive diagnostic tools for pediatric NAFLD: where are we now? Expert Rev Gastroenterol Hepatol 2020; 14:1035-1046. [PMID: 32715793 DOI: 10.1080/17474124.2020.1801413] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Nonalcoholic fatty liver disease (NAFLD) is a leading cause of liver disease in the pediatric population. It is a significant liver complication of obesity that also prominently affects children. Over the past decade, several noninvasive methods have been investigated for replacing liver biopsy to identify which children with NAFLD have nonalcoholic steatohepatitis (NASH) and fibrosis. These methods that aim to differentiate the type and extent of liver damage are based on two main different methodologies: a 'biological' approach centered on the quantification of circulating biomarkers; and a 'physical' approach established by analyzing different imaging data. AREAS COVERED In this review, we illustrate the state of the art and recent discoveries on noninvasive methods for the diagnosis of NAFLD, NASH, and advanced fibrosis. EXPERT OPINION Currently, noninvasive tests cannot diagnose NASH or determine the degree of fibrosis. However, several lines of evidence have suggested that if these tests are used in a complementary way with other laboratory tests and imaging they have the potential to be used to monitor progression of disease and response to therapy in pediatric NAFLD. Future scientific research will focus on combining these methods with multiple potential predictors of genetic susceptibility.
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Affiliation(s)
- Antonella Mosca
- Hepatology Gastroenterology and Nutrition, Bambino Gesù Children's Hospital , Rome, Italy
| | - Nadia Panera
- Research Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesù Children's Hospital, IRCCS , Rome, Italy
| | - Annalisa Crudele
- Research Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesù Children's Hospital, IRCCS , Rome, Italy
| | - Anna Alisi
- Research Unit of Molecular Genetics of Complex Phenotypes, Bambino Gesù Children's Hospital, IRCCS , Rome, Italy
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14
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Di Sessa A, Umano GR, Cirillo G, Marzuillo P, Arienzo MR, Pedullà M, Miraglia Del Giudice E. The rs72613567: TA Variant in the Hydroxysteroid 17-beta Dehydrogenase 13 Gene Reduces Liver Damage in Obese Children. J Pediatr Gastroenterol Nutr 2020; 70:371-374. [PMID: 31789772 DOI: 10.1097/mpg.0000000000002573] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
We first investigated in obese children the protective role of the hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) rs72613567:TA variant in liver damage. Six hundred eighty-five obese children were genotyped for HSD17B13, patatin-like phospholipase domain containing 3 (PNPLA3), transmembrane 6 superfamily member 2 (TM6SF2), and membrane bound O-acyltransferase domain containing 7 (MBOAT7) polymorphisms and underwent anthropometrical, ultrasonographic, and biochemical evaluation. Indirect measurement of liver fibrosis (Pediatric NAFLD Fibrosis Index [PNFI]) was calculated. The population was clustered in 2 genetic risk groups based on the numbers of steatogenic alleles (low: carriers up to 3 risk alleles, high: 4-6 risk alleles). Carriers of the HSD17B13 rare A allele showed lower percentage of hepatic steatosis and both lower serum transaminase and PNFI levels than noncarriers, even after adjustments for confounders. These findings were also confirmed in both risk groups. We demonstrated the protective effect of the rs72613567:TA HSD17B13 variant in reducing liver damage in obese children regardless of genetic predisposition.
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Affiliation(s)
- Anna Di Sessa
- Department of Woman, Child and of General and Specialized Surgery, University of Campania "Luigi Vanvitelli", Naples, Italy
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15
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Scudiero O, Pero R, Ranieri A, Terracciano D, Fimiani F, Cesaro A, Gentile L, Leggiero E, Laneri S, Moscarella E, Mazzaccara C, Frisso G, D'Alicandro G, Limongelli G, Pastore L, Calabrò P, Lombardo B. Childhood obesity: an overview of laboratory medicine, exercise and microbiome. Clin Chem Lab Med 2019; 58:1385-1406. [PMID: 31821163 DOI: 10.1515/cclm-2019-0789] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2019] [Accepted: 11/12/2019] [Indexed: 12/17/2022]
Abstract
In the last few years, a significant increase of childhood obesity incidence unequally distributed within countries and population groups has been observed, thus representing an important public health problem associated with several health and social consequences. Obese children have more than a 50% probability of becoming obese adults, and to develop pathologies typical of obese adults, that include type 2-diabetes, dyslipidemia and hypertension. Also environmental factors, such as reduced physical activity and increased sedentary activities, may also result in increased caloric intake and/or decreased caloric expenditure. In the present review, we aimed to identify and describe a specific panel of parameters in order to evaluate and characterize the childhood obesity status useful in setting up a preventive diagnostic approach directed at improving health-related behaviors and identifying predisposing risk factors. An early identification of risk factors for childhood obesity could definitely help in setting up adequate and specific clinical treatments.
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Affiliation(s)
- Olga Scudiero
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Naples "Federico II", Napoli, Italy.,CEINGE-Biotecnologie Avanzate, Naples, Italy
| | - Raffaela Pero
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Naples "Federico II", Napoli, Italy
| | - Annaluisa Ranieri
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Naples "Federico II", Napoli, Italy.,CEINGE-Biotecnologie Avanzate, Naples, Italy
| | - Daniela Terracciano
- Dipartimento di Scienze Mediche Traslazionali, Università degli Studi di Naples "Federico II", Napoli, Italy
| | - Fabio Fimiani
- Divisione di Cardiologia, Dipartimento di Scienze Cardiotoraciche e Respiratorie, Università della Campania "Luigi Vanvitelli", Naples, Italy
| | - Arturo Cesaro
- Divisione di Cardiologia, Dipartimento di Scienze Cardiotoraciche e Respiratorie, Università della Campania "Luigi Vanvitelli", Naples, Italy
| | | | | | - Sonia Laneri
- Dipartimento di Farmacia, Università degli Studi di Naples "Federico II", Napoli, Italy
| | - Elisabetta Moscarella
- Dipartimento di Scienze Mediche Traslazionali, Università della Campania "Luigi Vanvitelli", Caserta, Italy.,Unità di Cardiologia, Ospedale "Sant'Anna e San Sebastiano", Caserta, Italy
| | - Cristina Mazzaccara
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Naples "Federico II", Napoli, Italy.,CEINGE-Biotecnologie Avanzate, Naples, Italy
| | - Giulia Frisso
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Naples "Federico II", Napoli, Italy.,CEINGE-Biotecnologie Avanzate, Naples, Italy
| | - Giovanni D'Alicandro
- Centro di Medicina dello Sport e delle Disabilità, Dipartimento di Neuroscienze e Riabilitazione, AORN, Santobono-Pausillipon, Naples, Italy
| | - Giuseppe Limongelli
- Dipartimento di Scienze Mediche Traslazionali, Università della Campania "Luigi Vanvitelli", Caserta, Italy
| | - Lucio Pastore
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Naples "Federico II", Napoli, Italy.,CEINGE-Biotecnologie Avanzate, Naples, Italy
| | - Paolo Calabrò
- Dipartimento di Scienze Mediche Traslazionali, Università della Campania "Luigi Vanvitelli", Caserta, Italy.,Unità di Cardiologia, Ospedale "Sant'Anna e San Sebastiano", Caserta, Italy
| | - Barbara Lombardo
- Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Naples "Federico II", Napoli, Italy.,CEINGE-Biotecnologie Avanzate, Naples, Italy
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16
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Di Sessa A, Cirillo G, Guarino S, Marzuillo P, Miraglia del Giudice E. Pediatric non-alcoholic fatty liver disease: current perspectives on diagnosis and management. Pediatric Health Med Ther 2019; 10:89-97. [PMID: 31692530 PMCID: PMC6711552 DOI: 10.2147/phmt.s188989] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/07/2019] [Accepted: 08/13/2019] [Indexed: 12/14/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) represents the most common cause of chronic liver disease in childhood. To date, the "multiple-hit" hypothesis is largely recognized as an explanation of NAFLD pathogenesis and progression. Obesity and features of the metabolic syndrome have been closely linked to NAFLD development. Due to the increased prevalence of obesity worldwide, NAFLD has reached epidemic proportions over time. Given its unfavorable cardiometabolic burden (such as cardiovascular and metabolic consequences), it represents a worrying phenomenon needing a more comprehensive and successful management. Laboratory tests and classical imaging techniques play a pivotal role in NAFLD diagnosis, but novel noninvasive alternative methods to diagnose and monitor NAFLD have been investigated. Currently, lifestyle modifications remain the mainstay treatment, although its efficacy is poor because of the lack of compliance. Pediatric research is focusing on multiple alternative treatments targeting the main pathogenic factors such as insulin-resistance, dyslipidemia, gut-liver axis and microbiota, oxidative stress, and proinflammatory pathways. Results from these studies are promising but larger validation is needed. Innovative therapeutic approaches might add an important piece in the complex knowledge of pediatric NAFLD. We aimed to summarize recent insights into NAFLD diagnosis and treatment in children, with a focus on possible future perspectives in pediatric research.
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Affiliation(s)
- Anna Di Sessa
- Department of Woman, Child and General and Specialized Surgery, University of Studies of Campania “Luigi Vanvitelli”, Napoli80138, Italy
| | - Grazia Cirillo
- Department of Woman, Child and General and Specialized Surgery, University of Studies of Campania “Luigi Vanvitelli”, Napoli80138, Italy
| | - Stefano Guarino
- Department of Woman, Child and General and Specialized Surgery, University of Studies of Campania “Luigi Vanvitelli”, Napoli80138, Italy
| | - Pierluigi Marzuillo
- Department of Woman, Child and General and Specialized Surgery, University of Studies of Campania “Luigi Vanvitelli”, Napoli80138, Italy
| | - Emanuele Miraglia del Giudice
- Department of Woman, Child and General and Specialized Surgery, University of Studies of Campania “Luigi Vanvitelli”, Napoli80138, Italy
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17
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Li Q, Dhyani M, Grajo JR, Sirlin C, Samir AE. Current status of imaging in nonalcoholic fatty liver disease. World J Hepatol 2018; 10:530-542. [PMID: 30190781 PMCID: PMC6120999 DOI: 10.4254/wjh.v10.i8.530] [Citation(s) in RCA: 158] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/21/2018] [Revised: 06/25/2018] [Accepted: 06/28/2018] [Indexed: 02/06/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is the most common diffuse liver disease, with a worldwide prevalence of 20% to 46%. NAFLD can be subdivided into simple steatosis and nonalcoholic steatohepatitis. Most cases of simple steatosis are non-progressive, whereas nonalcoholic steatohepatitis may result in chronic liver injury and progressive fibrosis in a significant minority. Effective risk stratification and management of NAFLD requires evaluation of hepatic parenchymal fat, fibrosis, and inflammation. Liver biopsy remains the current gold standard; however, non-invasive imaging methods are rapidly evolving and may replace biopsy in some circumstances. These methods include well-established techniques, such as conventional ultrasonography, computed tomography, and magnetic resonance imaging and newer imaging technologies, such as ultrasound elastography, quantitative ultrasound techniques, magnetic resonance elastography, and magnetic resonance-based fat quantitation techniques. The aim of this article is to review the current status of imaging methods for NAFLD risk stratification and management, including their diagnostic accuracy, limitations, and practical applicability.
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Affiliation(s)
- Qian Li
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
| | - Manish Dhyani
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
- Department of Radiology, Lahey Hospital and Medical Center, 41 Burlington Mall Road, Burlington, MA 01805, United States
| | - Joseph R Grajo
- Department of Radiology, Division of Abdominal Imaging, University of Florida College of Medicine, Gainesville, FL 32610, United States
| | - Claude Sirlin
- Altman Clinical Translational Research Institute, University of California, San Diego, CA 92103, United States
| | - Anthony E Samir
- Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, United States
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18
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Valerio G, Maffeis C, Saggese G, Ambruzzi MA, Balsamo A, Bellone S, Bergamini M, Bernasconi S, Bona G, Calcaterra V, Canali T, Caroli M, Chiarelli F, Corciulo N, Crinò A, Di Bonito P, Di Pietrantonio V, Di Pietro M, Di Sessa A, Diamanti A, Doria M, Fintini D, Franceschi R, Franzese A, Giussani M, Grugni G, Iafusco D, Iughetti L, Lamborghini A, Licenziati MR, Limauro R, Maltoni G, Manco M, Reggiani LM, Marcovecchio L, Marsciani A, del Giudice EM, Morandi A, Morino G, Moro B, Nobili V, Perrone L, Picca M, Pietrobelli A, Privitera F, Purromuto S, Ragusa L, Ricotti R, Santamaria F, Sartori C, Stilli S, Street ME, Tanas R, Trifiró G, Umano GR, Vania A, Verduci E, Zito E. Diagnosis, treatment and prevention of pediatric obesity: consensus position statement of the Italian Society for Pediatric Endocrinology and Diabetology and the Italian Society of Pediatrics. Ital J Pediatr 2018; 44:88. [PMID: 30064525 PMCID: PMC6069785 DOI: 10.1186/s13052-018-0525-6] [Citation(s) in RCA: 140] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2018] [Accepted: 06/07/2018] [Indexed: 01/06/2023] Open
Abstract
The Italian Consensus Position Statement on Diagnosis, Treatment and Prevention of Obesity in Children and Adolescents integrates and updates the previous guidelines to deliver an evidence based approach to the disease. The following areas were reviewed: (1) obesity definition and causes of secondary obesity; (2) physical and psychosocial comorbidities; (3) treatment and care settings; (4) prevention.The main novelties deriving from the Italian experience lie in the definition, screening of the cardiometabolic and hepatic risk factors and the endorsement of a staged approach to treatment. The evidence based efficacy of behavioral intervention versus pharmacological or surgical treatments is reported. Lastly, the prevention by promoting healthful diet, physical activity, sleep pattern, and environment is strongly recommended since the intrauterine phase.
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Affiliation(s)
- Giuliana Valerio
- Department of Movement Sciences and Wellbeing, University of Naples Parthenope, via Medina 40, 80133 Naples, Italy
| | - Claudio Maffeis
- Pediatric Diabetes and Metabolic Disorders Unit, University of Verona, Verona, Italy
| | - Giuseppe Saggese
- Department of Pediatrics, University Hospital of Pisa, Pisa, Italy
| | | | - Antonio Balsamo
- Department of Medical and Surgical Sciences, University Hospital S.Orsola-Malpighi, Bologna, Italy
| | - Simonetta Bellone
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
| | | | - Sergio Bernasconi
- Italian Society for Pediatric Endocrinology and Diabetology (SIEDP), Parma, Italy
| | - Gianni Bona
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
| | - Valeria Calcaterra
- Pediatrics Unit, University of Pavia and Fondazione IRCCS Policlinico San Matteo, Pavia, Italy
| | | | - Margherita Caroli
- Italian Society for Obesity (SIO), Francavilla Fontana (Brindisi), Italy
| | | | - Nicola Corciulo
- Pediatric Unit, Hospital of Gallipoli, Gallipoli (Lecce), Italy
| | - Antonino Crinò
- Autoimmune Endocrine Diseases Unit, Bambino Gesù Children Hospital, IRCCS, Rome, Italy
| | - Procolo Di Bonito
- Department of Internal Medicine, “S. Maria delle Grazie”, Pozzuoli Hospital, Naples, Italy
| | | | - Mario Di Pietro
- Pediatric and Neonatal Unit, “G. Mazzini”Hospital, Teramo, Italy
| | - Anna Di Sessa
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Antonella Diamanti
- Artificial Nutrition Unit Bambino Gesù, Children’s Hospital, IRCCS, Rome, Italy
| | - Mattia Doria
- Italian Federation of Pediatricians (FIMP), Venice, Italy
| | - Danilo Fintini
- Endocrinology and Diabetology Unit Bambino Gesù Children Hospital, IRCCS, Rome, Italy
| | | | - Adriana Franzese
- Department of Translational Medical Science, Regional Center for Pediatric Diabetes, University Federico II of Naples, Naples, Italy
| | | | - Graziano Grugni
- Division of Auxology, Istituto Auxologico Italiano, IRCCS, Verbania, Italy
| | - Dario Iafusco
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Lorenzo Iughetti
- Pediatric Unit, University of Modena and Reggio Emilia, Modena, Italy
| | | | | | | | - Giulio Maltoni
- Department of Medical and Surgical Sciences, University Hospital S.Orsola-Malpighi, Bologna, Italy
| | - Melania Manco
- Research Area for Multifactorial Diseases, Children’s Hospital Bambino Gesù, Rome, Italy
| | | | | | | | - Emanuele Miraglia del Giudice
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Anita Morandi
- Pediatric Diabetes and Metabolic Disorders Unit, University Hospital of Verona, Verona, Italy
| | - Giuseppe Morino
- Nutrition Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy
| | | | - Valerio Nobili
- Department of Pediatrics and Infantile Neuropsychiatry, Sapienza University of Rome, Rome, Italy
- Hepatometabolic Unit, Bambino Gesù Children’s Hospital, IRCSS, Rome, Italy
| | - Laura Perrone
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | | | | | | | | | | | - Roberta Ricotti
- Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
| | - Francesca Santamaria
- Department of Translational Medical Science, Regional Center for Pediatric Diabetes, University Federico II of Naples, Naples, Italy
| | - Chiara Sartori
- Department of Obstetrics, Gynaecology and Paediatrics, Arcispedale S.Maria Nuova-IRCCS, Reggio Emilia, Italy
| | | | - Maria Elisabeth Street
- Department of Obstetrics, Gynaecology and Paediatrics, Arcispedale S.Maria Nuova-IRCCS, Reggio Emilia, Italy
| | - Rita Tanas
- Italian Society for Pediatric Endocrinology and Diabetology (SIEDP), Ferrara, Italy
| | | | - Giuseppina Rosaria Umano
- Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, Naples, Italy
| | - Andrea Vania
- Department of Pediatrics and Infantile Neuropsychiatry, Sapienza University of Rome, Rome, Italy
| | - Elvira Verduci
- Deparment of Pediatrics, San Paolo Hospital, University of Milan, Milan, Italy
| | - Eugenio Zito
- Department of Social Sciences, University of Naples Federico II, Naples, Italy
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19
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Di Sessa A, Umano GR, Cirillo G, Del Prete A, Iacomino R, Marzuillo P, Del Giudice EM. The Membrane-bound O-Acyltransferase7 rs641738 Variant in Pediatric Nonalcoholic Fatty Liver Disease. J Pediatr Gastroenterol Nutr 2018; 67:69-74. [PMID: 29601441 DOI: 10.1097/mpg.0000000000001979] [Citation(s) in RCA: 38] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND The rs641738 polymorphism in the membrane-bound O-acyltransferase domain containing protein 7 (MBOAT7) gene has been associated with increased risk of nonalcoholic fatty liver disease (NAFLD). OBJECTIVES To investigate the association between the MBOAT7 rs641738 polymorphism and both hepatic steatosis and biochemical markers of liver damage and to evaluate the potential additive effect of this variant and the I148M patatin-like phospholipase domain-containing 3 (PNPLA3) and the rs58542926 transmembrane 6 superfamily member 2 (TM6SF2) polymorphisms. METHODS One thousand and 2 obese children were genotyped for MBOAT7, PNPLA3, and TM6SF2 polymorphisms and underwent anthropometrical, ultrasonographic, and biochemical evaluation. Indirect measurement of liver fibrosis (Pediatric NAFLD Fibrosis Index [PNFI]) and a genetic risk score from these polymorphisms were calculated. RESULTS Carriers of the MBOAT7 T allele showed both higher alanine transaminase (ALT) (P = 0.004) and PNFI values (P = 0.04) than noncarriers. These findings were confirmed also for the carriers of the MBOAT7 T allele polymorphism with hepatic steatosis compared with noncarriers. A higher genetic risk score was associated with higher ALT (P = 0.011) and with an odds ratio (OR) to show elevated ALT of 3.4 (95% CI 1.3-5.5, P = 0.003). Patients belonging to genetic risk score 3 group had an OR to present steatosis of 2.6 (95% CI 1.43-4.83, P = 0.0018) compared with those belonging to lower genetic risk score group. CONCLUSIONS We first demonstrated in childhood obesity the role of the MBOAT7 rs641738 variant on serum ALT and the combined effect of the MBOAT7, PNPLA3, and TM6SF2 variants on NAFLD risk. We also provided the first pediatric association of the MBOAT7 polymorphism with indirect markers of liver fibrosis.
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Affiliation(s)
- Anna Di Sessa
- Department of Woman, Child and of General and Specialized Surgery, University of Campania "Luigi Vanvitelli," Naples, Italy
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20
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Sharma DL, Lakhani HV, Klug RL, Snoad B, El-Hamdani R, Shapiro JI, Sodhi K. Investigating Molecular Connections of Non-alcoholic Fatty Liver Disease with Associated Pathological Conditions in West Virginia for Biomarker Analysis. ACTA ACUST UNITED AC 2017; 8. [PMID: 29177105 PMCID: PMC5701750 DOI: 10.4172/2155-9899.1000523] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022]
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a disease characterized by a steatosis of the liver that may progress to more serious pathological conditions including: nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis. As the prevalence of NAFLD has increased worldwide in recent years, pathophysiology and risk factors associated with disease progression of NAFLD are at the focus of many studies. NAFLD is related to and shares common serum biomarkers with cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), obesity, and metabolic syndrome (MetS). West Virginia (WV) is a state with some of the highest rates of CVD, obesity and diabetes mellitus. As NAFLD is closely related to these diseases, it is of particular interest in WV. Currently there is no cost-effective, standardized method used clinically to detect NAFLD prior to the onset of reversible complications. At this time, the diagnosis of NAFLD is made with costly radiologic studies and invasive biopsy. These studies are only diagnostic once changes to hepatic tissue have occurred. The diagnosis of NAFLD by traditional methods may not allow for successful intervention and may not be readily available in areas with already sparse medical resources. In this literature review, we identify a list of biomarkers common among CVD, T2DM, obesity, MetS and NAFLD. From this research we propose the following biomarkers are good candidates for inclusion in a panel of biomarkers for the early detection of NAFLD: adiponectin, AST, ALT, apo-B, CK18, CPS1, CRP, FABP-1, ferritin, GGT, GRP78, HDL-C, IGF-1, IL-1β, 6, 8, 10, IRS-2PAI-1, leptin, lumican, MDA SREBP-1c and TNF-α. Creating and implementing a biomarker panel for the early detection and attenuation of NAFLD, prior to the onset of irreversible complication would provide maximum benefit and decrease the disease burden on the patients and healthcare system of WV.
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Affiliation(s)
- Dana L Sharma
- Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
| | - Hari Vishal Lakhani
- Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
| | - Rebecca L Klug
- Department of Surgery, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
| | - Brian Snoad
- Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
| | - Rawan El-Hamdani
- Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
| | - Joseph I Shapiro
- Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
| | - Komal Sodhi
- Department of Surgery, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA
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21
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Hamza RT, Ahmed AY, Rezk DG, Hamed AI. Dietary fructose intake in obese children and adolescents: relation to procollagen type III N-terminal peptide (P3NP) and non-alcoholic fatty liver disease. J Pediatr Endocrinol Metab 2016; 29:1345-1352. [PMID: 27442361 DOI: 10.1515/jpem-2016-0015] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/09/2016] [Accepted: 05/26/2016] [Indexed: 12/31/2022]
Abstract
BACKGROUND Excessive use of fructose has been incriminated as a risk factor for hepatic steatosis. Procollagen type III N-terminal peptide (P3NP) is a marker for steatohepatitis. Thus, we aimed to assess fructose intake in obese children and its relation to nonalcoholic fatty liver disease (NAFLD) and P3NP. METHODS Fifty-five obese children were compared to 30 controls. All were subjected to dietary fructose and anthropometric assessment, fasting blood sugar (FBS), fasting insulin (FI) and homeostasis model assessment of insulin resistance (HOMA-IR), lipid profile, uric acid, alanine aminotransferase (ALT), P3NP and abdominal ultrasound. RESULTS Patients had higher fructose intake which was associated with increased NAFLD grade. There was an increase in P3NP with increased NAFLD grade. P3NP correlated positively with fructose intake (processed sources and total) and caloric intake. CONCLUSIONS High fructose intake is associated with NAFLD and P3NP may serve as a marker of NAFLD in obese children with a proposed cutoff value of 8.5 ng/mL.
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Zhang TS, Qin HL, Wang T, Li HT, Li H, Xia SH, Xiang XH. Bibliometric analysis of top 100 cited articles in nonalcoholic fatty liver disease research. World J Hepatol 2016; 8:1478-1488. [PMID: 27957247 PMCID: PMC5124720 DOI: 10.4254/wjh.v8.i33.1478] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2016] [Revised: 08/10/2016] [Accepted: 09/22/2016] [Indexed: 02/06/2023] Open
Abstract
AIM To identify and assess the research situation of top 100 cited articles in nonalcoholic fatty liver disease (NAFLD).
METHODS The global scientific research articles in the Science Citation Index-Expanded relevant to NAFLD were retrieved and listed according to their citation times from the most to the least. The 100 most frequently cited original articles were selected to systematically evaluate their bibliometric parameters including times cited, publication year, journals, subject categories, and the highly related concepts of NAFLD, which reflected the history and current situation, publication distribution of leading countries and institutes as well as the research hotspots of NAFLD.
RESULTS Top 100 cited articles in NAFLD were published from 1965 to 2015 with a citation ranging of 227 to 2151 times since publication, in which the United States was the most predominant country and Mayo Clin was the most productive institution. The majority of the top 100 cited articles were concentrated in SCI subject category of Gastroenterology and Hepatology. Hepatology and Gastroenterology is the top journal that published over half 100 top-cited articles. The significant peak of top cited articles present in the first half of the 2000s while the highest mean number of citation presents in first half of the 1980s. In addition, concepts related to pathology characteristics, epidemiology and medicalization, metabolic syndrome and its combination of symptoms including insulin resistance, biomarkers of lipid metabolism and obesity are listed as the highly related concepts.
CONCLUSION The 100 top-cited articles marked with the leading countries, institutions, journals, hotspots and development trend in NAFLD field that could provide the foundation for further investigations.
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Della Corte C, Mosca A, Vania A, Alterio A, Alisi A, Nobili V. Pediatric liver diseases: current challenges and future perspectives. Expert Rev Gastroenterol Hepatol 2016; 10:255-65. [PMID: 26641319 DOI: 10.1586/17474124.2016.1129274] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Chronic liver diseases in children represent a rising problem with significant effects on public health. In fact, several pediatric liver diseases are precursors of adult chronic hepatopathies, cirrhosis and hepatocellular carcinoma. The prevalence of liver diseases in children is unknown. In the USA, every year, 15,000 children are hospitalized for liver diseases, but these disorders continue to be under-recognized or diagnosed late. The main reason is due to the frequent absence of symptoms in the vast majority of liver diseases, especially in the early stages. In the last few decades several advances have been made in understanding the pathogenesis of liver diseases, permitting the discovery of new therapeutic targets to treat liver diseases, thus improving the natural history of these disorders. In this article we discuss the most recent advances in the understanding of the pathogenesis, diagnosis and treatment of the most frequent pediatric liver diseases.
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Affiliation(s)
- Claudia Della Corte
- a Hepato-Metabolic Department , Bambino Gesù Children's Hospital, IRCCS , Rome , Italy
| | - Antonella Mosca
- b Center of Dietetics and Nutrition , Pediatric Clinic, 'La Sapienza' University , Rome , Italy
| | - Andrea Vania
- b Center of Dietetics and Nutrition , Pediatric Clinic, 'La Sapienza' University , Rome , Italy
| | - Arianna Alterio
- a Hepato-Metabolic Department , Bambino Gesù Children's Hospital, IRCCS , Rome , Italy
| | - Anna Alisi
- c Liver Research Unit , Bambino Gesù Children's Hospital, IRCCS , Rome , Italy
| | - Valerio Nobili
- a Hepato-Metabolic Department , Bambino Gesù Children's Hospital, IRCCS , Rome , Italy
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Orci LA, Gariani K, Oldani G, Delaune V, Morel P, Toso C. Exercise-based Interventions for Nonalcoholic Fatty Liver Disease: A Meta-analysis and Meta-regression. Clin Gastroenterol Hepatol 2016; 14:1398-411. [PMID: 27155553 DOI: 10.1016/j.cgh.2016.04.036] [Citation(s) in RCA: 155] [Impact Index Per Article: 17.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/09/2016] [Revised: 04/21/2016] [Accepted: 04/27/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS The burden of nonalcoholic fatty liver disease (NAFLD) is increasing worldwide. We performed a meta-analysis to determine the effectiveness of exercise-based lifestyle interventions on liver-specific end points in populations with NAFLD and underlying metabolic disorders such as obesity, type 2 diabetes, or metabolic syndrome. METHODS We searched PubMed-MEDLINE, Embase, and the Cochrane Central register through October 21, 2015 for randomized trials of exercise-based lifestyle interventions on end points such as intrahepatic lipid content and blood levels of alanine and aspartate aminotransferases. Effect sizes are reported as standardized mean difference and weighted mean difference values. To investigate heterogeneity, we performed sensitivity and meta-regression analyses. Results were reported according to the PRISMA statement. RESULTS We analyzed data from 28 trials. Physical activity, independently from diet change, was associated with a significant reduction in intrahepatic lipid content (standardized mean difference, -0.69; 95% confidence interval [CI], -0.90 to -0.48) and with reductions in alanine aminotransferase (weighted mean difference, -3.30 IU/L; 95% CI, 5.57 to -1.04) and aspartate aminotransferase (weighted mean difference, -4.85 IU/L; 95% CI, -8.68 to -1.02). By meta-regression, we found individuals with increasing body mass index to be increasingly more likely to benefit from the intervention (beta coefficient = -0.10; P = .037). We recorded no effect modification by variables related to the intensity of the intervention. CONCLUSIONS In a meta-analysis of randomized trials, we found strong evidence that physical activity reduces intrahepatic lipid content and markers of hepatocellular injury in patients with NAFLD. This effect correlated with baseline body mass index.
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Affiliation(s)
- Lorenzo A Orci
- Division of Abdominal and Transplantation Surgery, Department of Surgery, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland; Hepato-pancreato-biliary Centre, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland.
| | - Karim Gariani
- Division of Clinical Endocrinology, Department of Medical Specialties, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Graziano Oldani
- Division of Abdominal and Transplantation Surgery, Department of Surgery, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland; Hepato-pancreato-biliary Centre, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Vaihere Delaune
- Division of Abdominal and Transplantation Surgery, Department of Surgery, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland; Hepato-pancreato-biliary Centre, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Philippe Morel
- Division of Abdominal and Transplantation Surgery, Department of Surgery, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland; Hepato-pancreato-biliary Centre, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
| | - Christian Toso
- Division of Abdominal and Transplantation Surgery, Department of Surgery, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland; Hepato-pancreato-biliary Centre, Geneva University Hospitals and Faculty of Medicine, University of Geneva, Geneva, Switzerland
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Sodhi K, Bracero L, Feyh A, Nichols A, Srikanthan K, Latif T, Preston D, Shapiro JI, Elitsur Y. Role of Serum Biomarkers in Early Detection of Non-Alcoholic Steatohepatitis and Fibrosis in West Virginian Children. ACTA ACUST UNITED AC 2016; 7. [PMID: 27182456 PMCID: PMC4866601 DOI: 10.4172/2155-9899.1000393] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Background Obesity, an epidemic among West Virginia children, as well as insulin resistance (IR), is well-established contributors to nonalcoholic steatohepatitis (NASH). Progression of NASH can lead to hepatic fibrosis and cirrhosis, making early detection imperative. The standard for diagnosing NASH is histologically via liver biopsy, which is highly invasive and generally contraindicated in children. By studying serum biomarkers associated with NASH, we aim to identify high risk children who can benefit from a less invasive, alternative approach to the early detection of NASH. Methods Seventy one children were prospectively recruited and divided into 3 groups: normal weight without IR (control), obese without IR, and obese with IR. Serum samples were drawn for each patient and biomarker levels were assessed via ELISA kits. Results Obese without IR and obese with IR patients had significantly elevated levels of lipid metabolism and accumulation markers (FGF-21, NEFA, FATP5, ApoB), oxidative stress markers (dysfunctional HDL, 8-Isoprostane), inflammatory markers(dysfunctional HDL, CK-18) and apoptosis markers (CK-18) compared to control patients (p<0.02). Bilirubin (an antioxidant) was significantly decreased in the obese without IR and obese with IR patients compared to control (p<0.02). Conclusion This study showed a correlation between obesity, IR, and biomarkers associated with NASH in pediatrics patients from West Virginia, with obese with IR patients showing the strongest correlation. These findings support the clinical application of these serum biomarkers as a less invasive method for early detection of NASH and hepatic fibrosis.
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Affiliation(s)
- Komal Sodhi
- Department of Surgery and Pharmacology, Joan C. Edwards School of Medicine, Marshall University, USA
| | - Lucas Bracero
- Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, USA
| | - Andrew Feyh
- Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, USA
| | - Alexandra Nichols
- Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, USA
| | - Krithika Srikanthan
- Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, USA
| | - Tariq Latif
- Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, USA
| | - Deborah Preston
- Department of Pediatrics, Division of Gastroenterology, Joan C. Edwards School of Medicine, Marshall University, USA
| | - Joseph I Shapiro
- Department of Surgery and Pharmacology, Joan C. Edwards School of Medicine, Marshall University, USA
| | - Yoram Elitsur
- Department of Pediatrics, Division of Gastroenterology, Joan C. Edwards School of Medicine, Marshall University, USA
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